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AMPK→reduced amyloid-β and tau phosphorylation
Metformin reduces amyloid-beta production and tau phosphorylation via AMPK activation, and Mendelian randomization studies suggest metformin targets genuinely reduce Alzheimer's disease risk in the general population. Evidence is extensive with 32 papers up to 2025, including clinical trials of intranasal metformin for cognitive impairment.
“Evaluating the efficacy and mechanism of metformin targets on reducing Alzheimer's disease risk in the general population: a Mendelian randomisation study.”
— Evaluating the efficacy and mechanism of metformin targets on reducing Alzheimer's disease risk in the general population: a Mendelian randomisation study. (2022)DOI“Evaluating the efficacy and mechanism of metformin targets on reducing Alzheimers disease risk in the general population: a Mendelian randomization study”
— Evaluating the efficacy and mechanism of metformin targets on reducing Alzheimers disease risk in the general population: a Mendelian randomization study (2022)DOI“The present study investigated the effect and mechanism of action of intranasal metformin treatment on impaired cognitive functions in an experimental mice model of AD.”
— Intranasal metformin treatment ameliorates cognitive functions via insulin signaling pathway in ICV-STZ-induced mice model of Alzheimer's disease. (2022)DOI“Novel therapeutic mechanism of action of metformin and its nanoformulation in Alzheimer's disease and role of AKT/ERK/GSK pathway.”
— Novel therapeutic mechanism of action of metformin and its nanoformulation in Alzheimer's disease and role of AKT/ERK/GSK pathway. (2022)DOI“Current study explored the therapeutic mechanism of metformin (insulin sensitizer) and its solid-lipid nanoformulation (SLN) in rat-model of AD.”
— Novel therapeutic mechanism of action of metformin and its nanoformulation in Alzheimer's disease and role of AKT/ERK/GSK pathway. (2022)DOI“It is concluded that Lupeol and Metformin has shown efficacy in dementia with possible synergism between the two and can be explored as potential therapeutic agents for managing dementia of Alzheimer's disease (AD) type.”
— Beneficial effect of lupeol and metformin in mouse model of intracerebroventricular streptozotocin induced dementia. (2024)DOI